N-乙酰-L-半胱氨酸对小鼠急性酒精性脂肪肝的保护作用
Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases(2018)
摘要
Objective: To investigate the roles of N-acetyl-L-cysteine (NAC) against binge drinking-induced fatty liver in mice. Methods: SPF male C57BL/6 mice were randomly divided into 3 groups, i.e. control group, model group, and NAC/ethanol group (n=10). Mice in model and NAC/ethanol groups were exposed to 3 doses of ethanol (6 g/kg bw) to induced fatty liver, while mice in control group received equal volume and equal energy of maltodextrin solution. NAC was administered to mice at 1 h before ethanol exposure (100 mg/kg bw, i.p.). The mice were sacrificed at 6 h after the last ethanol exposure. The liver and epididymal adipose tissues were collected. Histopathological examination and biochemical assay kit were used to evaluate the fat accumulation, while Western-blot was performed to detect the protein levels of some key factors involved in fat metabolism in liver and adipose tissues. Results: Compored with control group mice, the liver index and liver weight were significantly increased compared with model group, the liver index and TG level in NAC/ethanol group mice were all significantly decreased (P<0.05). Histological examination showed NAC effectively suppressed binge drinking-induced fat accumulation in mice liver. In addition, NAC had no significant effects on the protein levels of peroxisome proliferator-activated receptor-α (PPAR-α), Acy-CoA oxidase (ACOX), sterol regulatory element binding protein 1 c (SREBP-1c) and fatty acid synthase (FAS). Furthermore, the protein levels of hormone sensitive lipase (HSL) did not significantly differ among 3 groups, whereas NAC prevented binge drinking-induced increase of HSL phosphorylation at ser563 and ser660. Conclusion: NAC could effectively attenuate binge drinking-induced fatty liver, which might be associated with the inhibition of lipid mobilization by suppressing the phosphorylation of HSL.目的: 研究抗氧化剂N-乙酰-L-半胱氨酸(N-acetyl-L-cysteine,NAC)对小鼠酒精性脂肪肝(alcoholic fatty liver,AFL)的保护作用。 方法: SPF级雄性C57BL/6小鼠随机分为对照组、模型组及NAC干预组,每组10只。模型组及NAC干预组小鼠连续灌胃给予3次6 g/kg乙醇口服诱导急性AFL,对照组小鼠给予等体积等能量的麦芽糖糊精溶液。NAC在每次乙醇染毒前1 h腹腔注射给予100 mg/kg。末次乙醇染毒后6 h,处死小鼠取肝脏和附睾脂肪组织;病理学检查肝脏脂肪蓄积情况,生化试剂盒测定肝脏甘油三酯(triglyceride,TG)含量;Western-blot测定相关蛋白的表达。 结果: 与对照组小鼠比较,模型组小鼠肝脏明显增大,肝重及肝脏系数明显增加,差异有统计学意义(P<0.05)。与模型组比较,NAC干预组小鼠肝脏系数和肝组织TG含量明显降低,差异有统计学意义(P<0.05)。病理学检查结果显示,模型组小鼠肝脏切片中有大量橙红色的脂滴,而NAC干预组小鼠肝脏切片中脂肪滴明显减少。与模型组比较,NAC干预组小鼠肝脏中过氧化物酶体增殖物活化受体α(PPAR-α)、乙酰辅酶A氧化酶(ACOX)略有减少,固醇调节元件结合蛋白-1c(SREBP-1c)、脂肪酸合成酶(FAS)的蛋白含量无明显改变。附睾脂肪中激素敏感性脂肪酶(HSL)总蛋白在3组小鼠之间未见明显差异。NAC干预组小鼠脂肪组织中p-HSL(ser563)和p-HSL(ser660)的蛋白含量较模型组小鼠明显降低,差异有统计学意义(P<0.05)。 结论: 预先给予NAC可以明显减轻急性乙醇染毒导致的小鼠肝脏中TG的蓄积,其作用可能与抑制外周脂肪动员有关。.
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关键词
Alcoholic fatty liver,HSL,N-acetyl-L-cysteine,PPAR-α,SREBP-1c
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